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Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

Abstract

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats1,2,3,4. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.

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Figure 1: Nogo sequence and messenger RNA expression.
Figure 2: Nogo protein in the adult CNS.
Figure 3: Antisera raised against recombinant Nogo protein neutralize myelin-derived inhibitory activity.
Figure 4: Growth of DRG neurites into adult myelinated optic nerve explants10 in the presence of AS 472.
Figure 5: Recombinant Nogo-A is inhibitory and is recognised by mAb IN-1.

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Acknowledgements

We thank T. Oertle and C. Bandtlow for suggestions and discussions; T. Flego for technical assistance; R. Schöb and E. Hochreutener for help with the Figures; and C. Brösamle for critically reading the manuscript. This study was supported by grants from the Swiss National Science Foundation, the Maurice E. Muller Foundation (Berne), the International Research Institute for Paraplegia (Zurich) and the Spinal Cord Consortium of the Christopher Reeve Paralysis Foundation (Springfield, New Jersey).

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Chen, M., Huber, A., van der Haar, M. et al. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403, 434–439 (2000). https://doi.org/10.1038/35000219

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